Human Leukocyte Antigen-C and Haplotypes: Associations with Resistance and Susceptibility to HIV-1 Infection among Serodiscordant Couples in Nigeria

Abstract

INTRODUCTIONThe Human Leucocyte Antigen (HLA) class-1 is known to play a significant role in mediating resistance or susceptibility to HIV infection in the clinical course of AIDS. Recent studies have identified HLA-C as a key molecule that affects HIV disease progression. However, the role of HLA class 1 in heterosexual HIV-1 susceptibility or resistance in serodiscordant couples is not known in Nigeria. Therefore, this study evaluated the association between HLA-C susceptibility and resistance in HIV-1 transmission amongst heterosexual serodiscordant couples in Nigeria.METHODSA total of 271 serodiscordant, concordant HIV positive and negative couples who gave informed consent were enrolled into this study. Extracted genomic DNA was sequenced for high resolution HLA-C class 1 genotypes using allele-specific primers (on exons 2 and 3) for HLA-C sequencing and typing.RESULTSThe highest frequency distribution of high-resolution HLA-C alleles observed in the HIV positive subjects were: HLA-C*040101 178 (35.0%) followed by C*0701 124 (24.9%) compared with HIV negative subjects: C*040101 108(39.0%) followed by C*0701 64(24.7%). Alleles C*070201 (OR = 4.19, P<0.05) and C*0804 (OR = 3, P<0.045) were found to be independently associated with HIV-1 susceptibility in the cohort of serodiscordant couples. HLA-C*0802 (OR=0.5. P<0.005) and C*0304 (OR=0.34. P<0.002) were significantly associated with HIV-1 resistance to HIV-1 infection among the cohort.CONCLUSIONThe result has contributed to the importance of how host HLA-C genetic factors can influence HIV-1 disease susceptibility (HLA-C*070201; C*0804) and resistance (HLA-C*0802; C*0304) in serodiscordant couples. This information may contribute to the development of future effective HIV vaccine in Nigeria.